Present understanding of antibodies and their related genes is based almost entirely on information derived from a few mammalian species. The overall goal of this research program is to increase our understanding of the range of diversity in the vertebrate immune system. These investigations may also clarify aspects of the immune response in mammals. Much of our recent work has focussed on the immune system of the amphibian, Xenopus laevis, a classical model for vertebrate development. One objective is to elucidate the genomic organization of a recently identified immunoglobulin light chain family in Xenopus. This family is particularly interesting because it is very different in sequence from all known light chains. Examination of the genes encoding these light chains may provide insight into evolutionary relationships, which are not apparent from sequence comparisons. The developmental sequence of gene rearrangement events in the formation of immunoglobulin and T cell receptor molecules will also be examined. To this end, we have identified the Xenopus homologues of two genes, RAG-1 and RAG-2, which have a critical role in this process. Studies of their expression should help to define developmental lineages of B and T lymphocytes in this species. These studies may also elucidate the molecular basis for changes in the immune response that accompany metamorphosis. Although immunoglobulin genes have been characterized in considerable detail, genes encoding Xenopus T cell receptors have not yet been identified. Therefore, isolation and characterization of these receptors is an important objective. To date, there is no definitive evidence for an inducible immune response in the most primitive vertebrate group, the Agnatha (jawless fish). Since our studies indicate that RAG-1 is a highly conserved gene from sharks to mammals, it may be more easily identified than the more divergent immunoglobulin genes. We will, therefore, determine whether RAG-1 is present in representative Agnatha (hagfish and lamprey); its identification would justify renewed efforts to characterize the immune system of these primitive vertebrates.